“Pancreatic exocrine function tests” are useful for the diagnosis of pancreatic diseases such as chronic and acute pancreatitis and pancreatic cancer. They are also useful for the ascertainment of the condition of a disease, the management of medication and the assessment of the prognosis of a disease in a patient. (As for the general review, see Arvanitakis and Cooke, Gastroenterology, 74:932 (1978); Niederau and Grendell, Gastroenterology, 88:1973 (1985); Goldberg, Bull. Mol. Biol. Med., 15:1 (1990); Lankisch, Int. J. Pancreatology, 14:9 (1993); Bank and Chow, Gastroenterologist, 2:224. (1994); and Steer et al., New Eng. J. Med., 332:1482 (1995).
The standard method for pancreatic exocrine function tests is one which involves inserting a tube through the mouth to the duodenum to collect the duodenal juice. At present, the secretin test is commonly used wherein secretin is intravenously administered to stimulate the secretion of the pancreatic juice prior to the collection. This method is highly accurate since the amounts and components of the pancreatic juice are directly analyzed. However, this method can not be used repeatedly or used for screening because of the very strong stress caused on the patients. It is only available in a relatively small number of medical facilities staffed with highly skilled physicians. Further, since this method requires fluoroscopic tube placement during the collection of the duodenal juice, there is a problem of X ray exposure.
Hence, in repeated or screening tests, simpler methods have been used which require no intubation. At present, the following four methods are mainly used:
1. PFD test wherein a synthetic substrate BT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzoic acid) for chymotrypsin secreted from the pancreas is orally administered and the urinary excretion of PABA (p-aminobenzoic acid), the product of degradation by chyrnotrypsin, is determined;
2. PLT test wherein a synthetic substrate EDL (fluorescein dilaurate) for cholesterol ester hydrolase, esterase, secreted from the pancreas is orally administered and the urinary excretion or the blood level of the degradation product fluorescein is determined;
3. Fecal chymotrypsin test wherein chymotrypsin in the feces is quantitatively determined; and
4. Fecal elastase test wherein elastase in the feces is quantitatively determined.
However, the sensitivity of any of these tests is too low to detect slight decreases in pancreatic exocrine function.
Furthermore, the PFD and PLT tests require a long time to carry out and therefore cannot often be performed on outpatients and are not suitable in physical examinations or the like.
To solve these problems, a number of simpler pancreatic exocrine function tests have been reviewed. 13C-breath tests have also been applied wherein a 13C-labeled compound is administered and an increase in the concentration of 13CO2 in the breath is determined. The following tests may be listed:
1. 13C-breath test wherein a 13C-labeled lipid or mixed triglyceride, which is a substrate for lipase, is administered (Chen et al., J. Nuclear Med., 15:1125 (1974); Watkins et al., J. Lab. Clin. Med., 90:422 (1977); Ghoos et al., Digestion, 22:239 (1981); John, S G., Gastroenterology, 83:44 (1982); Watkins et al., Gastroenterology, 82:911 (1982); Benini et al., Digestion, 29:91 (1984); Jones et al., J. Lab. Clin. Med., 105:647 (1985); Knoblach et al., Monatsschr Kinderheilkd, 136:26 (1988); Vantrappen et al., Gastroenterology, 96:1126 (1989); Murphy et al., Arch. Disease in Childhood, 65:574 (1990); Kato et al., Am. J. Gastroenterol., 88:64 (1993); McClean et al., Arch. Disease in Childhood, 69:366 (1993); Jakobs et al., Eur. J. Pediatr., 156:S78 (1997); and Kalivianakis et al., Eur. J. Clin. Invest., 27:434 (1997));
2. 13C-breath test wherein a 13C-labeled cholesterol ester, which is a substrate for cholesterol esterase, lipase, is administered (Mundlos, et al., Pediatric Res., 22:257 (1987); Cole et al., Gastroenterology, 93:1372 (1987); and Mundlos et al., Gut, 31:1324 (1990));
3. 13C-breath test wherein a 13C-labeled starch, which is a substrate for amylase, is administered (Hiele et al., Gastroenterology, 96:503 (1989); Dewit et al., Pediatric Res., 32:45 (1992); and Z. Gastroenterol., 35:187 (1997));
4. 13C-breath test wherein a 13C-enriched egg protein, which is a protein having the 13C-concentration increased from the natural abundance of 1.1 atm % up to 1.4 atm % by feeding a chicken with 13C-leucine and which is a substrate for protease, is administered (Y. Ghoos, 13CO2-Breath Tests at the laboratory “tigestion-Absorption”, University Hospital Gasthuisberg, Leuven, Belgium (1996)); and
5. breath test wherein a 13C-labeled peptide (Japanese Unexamined Patent Application Publication No. 2000-053697), a 13C-labeled fluorescein ester compound (Japanese Unexamined Patent Application Publication No. 2000-159773) or a 13C-labeled oligosaccharide or a cyclodextrin/13C-labeled compound clathrate inclusion complex (Japanese Unexamined Patent Application Publication No. 2000-159810) is administered.
However, the methods 1 to 4 are also low in sensitivity and time-consuming. Therefore, these methods have not been established in clinical fields. In the method 5, the 13C-labeled compounds currently used in the test are expensive.
Under these situations, development of a simple pancreatic exocrine function test that imparts low stress on a subject, is less costly and gives accurate results in a short time has been demanded.
Thus, it is an object of the present invention to provide a diagnostic preparation for the diagnosis of pancreatic exocrine function which allows a simple, highly sensitive pancreatic exocrine function test that imparts low stress on a subject, is less costly and gives accurate results in a short time.
It is another object of the present invention to provide a new drug delivery system and enteric preparation.